1. Azienda Ospedaliero-Universitaria, Arcispedale S. Anna,
Potential value of CT Perfusion maps in differentiating high grade glioma recurrence from radiation necrosis
Enrico Fainardi1, Vania Ramponi2, Benedetta Urbini3, Massimo Borrelli1, Andrea Saletti1, Andrea Bernardoni1, Pierluigi Api4, Roberta Schivalocchi2, Francesco Cartei4, Michele Cavallo2, Stefano Ceruti1, Riccardo Tamarozzi1
1Unità Operativa di Neuroradiologia, 2Unità Operativa di Neurochirurgia, 3Unità Operativa di Oncologia, 4Unità Operativa di Radioterapia Oncologica,
Azienda Ospedaliero-Universitaria, Arcispedale S. Anna,
Ferrara (Italy)

2. Background
Gd T1
PWI CBV
Magnetic Resonance Perfusion-Weighted Imaging (MR-PWI) is able to demonstrate tumor angiogenesis in high grade gliomas = increase in cerebral blood volume (CBV) and blood-brain barrier permeability

3. Background
Gd T1
PWI CBV
Gd T1
PWI CBV
Recurrence
Radiation necrosis
MR-PWI can help to distinguish between tumor progression and post-treatment radiation effects

4. Aim Computed Tomography Perfusion (CTP):
CECT
CBF
CBV PS
Computed Tomography Perfusion (CTP):
can identify increased vascularity related to high grade gliomas
is faster and easier to perform than MR-PWI
has the potential to discriminate between high grade glioma recurrence and radiation necrosis

5. Patients
Twenty-seven patients (19 male and 8 female; mean age ± SD = 56.1 ± 11.7 years; Karnofsky performance status range = %):
histopathological diagnosis of high grade gliomas (24 WHO grade IV glioblastoma multiforme and 3 WHO grade III anaplastic astocytoma)
underwent surgery, radiation therapy and adjuvant chemotherapy
developed new or progressive enhancing lesions in the radiation field on follow-up MRI scans (mean time period ± SD = 6.9 ± 6.7 months) after radiation treatment

6. Categorization
Tumor recurrence was defined as the presence of progressive clinical deterioration and a size increasing of MRI abnormal brain tissue = 18 patients
Radiation necrosis was classified as the occurrence of stabilization or improvement in clinical conditions and MRI brain lesion = 9 cases

7. CTP studies
CTP studies were performed by using a single-section CT scanner (CT Hispeed ZX/i; GE Medical System, Waukesha, Wis):
a series of 45 CT scans acquired in a single slice (10-mm slice thickness, 80 kVp; 200 mAs; matrix 512 x 512; FOV 25-cm; total scan time 50 sec) during the automatic injection of 50 ml of non-ionic contrast agent at the rate of 3.5 ml/sec, starting 5 seconds before the initial image
the single slice was located at the level containing the largest volume of abnormal tissue

8. CTP maps
CBF
CBV
MTT PS
Perfusion maps were generated for each patient (CT Perfusion 3 and 4, GE Medical System, Waukesha, Wis) with:
a deconvolution-based algorithm (CBF = ml/100g/min; CBV = ml/100g; MTT = sec)
an adiabatic approximation of distributed parameter analysis (PS = ml/100g/min)
large blood vessels were automatically excluded by the calculation

9. CTP mapping
(1)
(2)
Two different region of interest (ROIs) were manually drawn on the baseline diagnostic CT scan:
1) the enhancing new-formed tissue;
2) an area of normal appearing brain tissue mirroring the abnormal region and located in the contralateral hemisphere
The corresponding T1-enhanced MRI was used to correctly localize enhancing lesions

10. CTP measurements
CBF
CBV
MTT PS
Regional absolute levels of CBF (rCBF), CBV (rCBV), MTT (rMTT) and PS (rPS) in both injured and apparently normal tissue
Normalized ratios of CBF (nCBF), CBV (nCBV), MTT (nMTT) and PS (nPS) by dividing lesioned and contralateral absolute levels

11. Statistics
2+3+7/4 x 35 + √ 5 = ?
After checking data for normality (Kolmogorov-Smirnov test), statistical analysis was performed by Mann-Whitney U test
A value of p < 0.05 was considered as statistically significant

12. Enhancing tissue vs. contralateral area
rCBF and rCBV levels were higher in enhancing than in contralateral areas for patients with tumor recurrence

13. Enhancing tissue vs. contralateral area
rPS values were more elevated in lesioned than in apparently normal areas for patients with tumor recurrence and, with a lesser extent, with radiation necrosis

14. Recurrence vs. radiation necrosis
rCBF, rCBV and rPS levels in enhancing tissue were higher in patients with tumor recurrence than in those with radiation necrosis

15. Recurrence vs. radiation necrosis
nCBF, nCBV and nPS levels were higher in patients with tumor recurrence than in those with radiation necrosis

16. Drawbacks
CBF
patient population was small (the identification of CTP threshold values was difficult)
patient selection was not based on histopathological findings
PS maps were not generated after delayed acquisition (normalized values were calculated)
limited coverage
radiation exposure (low with a single slice protocol)
contrast material administration (generally safe)
CBV PS

17. Conclusions
CBF
CTP is efficient in detecting angiogenesis associated with tumor recurrence represented by a combination of increased CBF, CBV and PS levels
Radiation necrosis can be characterized by a slightly elevation of PS levels related to a possible subacute ischemia
Multi-parametric CTP approach is a promising tool for differentiating high grade glioma progression from post-treatment radiation effects
CBV PS

18. This study was presented on behalf of:
Project of Emilia-Romagna region in Neuro-Oncology